These days, a number of detection and analysis methods for determining physiological parameters in body fluid samples or other biological samples are performed in an automated manner and in large numbers in automatic analysis devices, also so-called in vitro diagnostic systems.
Current analysis devices are able to perform a multiplicity of detection reactions and analyses using a sample. In order to be able to perform a multiplicity of examinations in an automated manner, various apparatuses for the spatial transfer of measurement cells, reaction containers, and reagent containers are required, such as, e.g., transfer arms with a gripper function, transport belts or rotatable transport wheels, and apparatuses for transferring liquids, such as, e.g., pipetting apparatuses. The devices comprise a control unit which, by means of appropriate software, is able to plan and work through the work steps for the desired analyses in a largely independent manner.
Many of the analysis methods used in such analysis devices with automated operation are based on optical processes. The determination of clinically relevant parameters, such as, e.g., the concentration or activity of an analyte, is often implemented by virtue of part of a sample being mixed with one or more test reagents in a reaction vessel, which can also be the measurement cell, as a result of which a biochemical reaction or a specific binding reaction is initiated, bringing about a measurable change in an optical or other physical property of the test mix.
In addition to spectrophotometry, nephelometry is a widely used analysis process. By way of example, nephelometry renders it possible to determine the concentration of finely distributed, colloidal particles in liquids or gases quantitatively. If a suspension of small particles is introduced into a light beam, part of the entering light is absorbed. Another part, which is also referred to as a primary beam, leaves the suspension without being scattered, and a further part is scattered laterally in relation to the entering beam. In nephelometry, this laterally emerging scattered light is measured.
Nephelometry is predominantly used for the quantitative or qualitative detection of analytes, such as, e.g., proteins, which are detectable by means of a specific binding reaction between specific binding partners, e.g., by means of an antigen/antibody binding.
A nephelometry system comprises at least one light source, at least one photodetector and at least one receptacle position for a measurement cell. Typically, the arrangement of light source and light detector is selected in such a way that the scattered light is measurable, wherein scattered light is scattered by macromolecules to be detected in the sample, e.g., by particle aggregates which are produced as a result of an analyte-dependent reaction in a reaction mix.
Different set-ups are commercially available, which differ in terms of the arrangement of light source, receptacle position for the measurement cell, and photodetector. By way of example, in one set-up, the photodetector can be arranged laterally from the light beam emitted by the light source in order to register the scattered light in an angle range of 90° in relation to the direction of the light beam emitted by the light source. This is advantageous in that the intensity of the scattered light can be relatively low and the influence of the measurement by the non-scattered part of the light beam emitted by the light source, which is referred to as primary beam, is relatively small.
In another set-up, light source, receptacle position, and photodetector can be arranged in such a way that the photodetector registers the scattered light in the angle ranges around the propagation direction of the light beam emitted by the light source in which the intensity of the scattered light is relatively high. However, not only the scattered light but also the primary beam reaches the photodetector in this geometry. However, since only the scattered part of the light is intended to contribute to the measurement result, complete blocking of the primary beam is required for an optimization of the measurement result.
Optical stops are usually used to block the primary beam. These are held in the beam path by means of thin attachments, such as, e.g., wires, and adapted in terms of the size and shape thereof in such a way that they preferably completely block the primary beam such that, where possible, only scattered light is incident on the detector. Preferably, the ratio of scattered light portions to primary beam portions is less than 0.001.
Analysis devices in which either the optical unit is movable relative to the measurement cells or in which the measurement cells are movable relative to the optical unit are becoming more widespread. This is advantageous in that a multiplicity of samples can be examined virtually simultaneously by using one optical unit, significantly increasing the sample throughput.
EP-A1-2309251 has described an apparatus for the photometric examination of samples, in which the measurement cells have a stationary embodiment and are arranged in a circular arc-shaped manner, while the optical unit moves along the measurement cell arrangement in a circular arc-shaped manner.
In such optical systems, in which the optical unit is moved relative to the measurement cell (or vice versa), the light beam travels along a route, preferably across the measurement cell, and a plurality of measurement values are registered, wherein each individual measurement value originates from a different position in the measurement cell due to the movement. As a result, a typical, well-shaped curve (see FIG. 1) with a first, falling flank, a curve base, and a second, rising flank is generated in nephelometric measurements. When the measurement cell enters into (falling flank) and exits from (rising flank) the primary beam, the light of the primary beam is incident on the measurement cell walls, reflected or refracted and guided past the stop, which is in fact intended to block the primary beam, to the photodetector. The significant region for determining the analyte lies in the region of the curve base, where the blocking of the primary beam is at a maximum. Furthermore, there is a change in respect of the location of the scattering volume in the measurement cell between subsequent measurements in time of the same sample as a result of mechanical tolerances of the moving portion, which is important if, for example, reaction kinetics are intended to be registered.